- Finalization of the study report on the double-blind,
placebo-controlled Phase 1 trial of OPM-101 in 104 healthy
volunteers (HV) who received OPM-101
- 24-hour ECG analysis reveals no toxic effect of OPM-101 on
cardiac parameters
- In an ex vivo whole blood study, OPM-101 rapidly and
completely inhibited the stimulated release of TNFα, a downstream
marker of RIPK2 pathway activation, indicating a strong
pharmacological immunomodulatory effect
- PK/PD modeling predicts that a concentration of OPM-101
between 100 and 300 ng/mL would achieve target inhibition of at
least 80% over the entire treatment period
- The favorable safety, pharmacokinetics and pharmacodynamics
of OPM-101 support the pursuit of its clinical development for the
treatment of diseases caused by deregulation of the pathway
involving its therapeutic target, the RIPK2 kinase
- Phase 1b/2a clinical trial protocol to be filed in the
fourth quarter of 2024 for launch in early 2025
Regulatory News:
Oncodesign Precision Medicine (OPM) (ISIN: FR001400CM63;
Mnemonic: ALOPM), a biopharmaceutical company specializing in
precision medicine for the treatment of resistant and metastatic
cancers, today confirms and details the final results of its Phase
1 clinical trial with OPM-101, its RIPK2 inhibitor and drug
candidate administered orally to healthy volunteers, first reported
on July 16, 2024. This clinical trial began in February 2023, the
database was frozen in June 2024, and the full results and final
study report became available, as scheduled in the study timetable,
in October 2024.
OPM-101 is an experimental, powerful and selective small
molecule inhibitor of the RIPK2 kinase. OPM-101 is designed to
modulate the pro-inflammatory signal transmission pathway of this
kinase, which is responsible for the development of inflammatory
diseases, and has the potential to treat diseases in the fields of
IBD (Chronic Inflammatory Bowel Disease) and immuno-oncology.
This randomized, double-blind, placebo-controlled phase 1 study
was designed to evaluate the safety, tolerability, pharmacokinetics
and pharmacodynamics of OPM-101 (EudraCT: 2022-003122-50) in 104
healthy volunteers:
- In the SAD part of the trial, 72 HV (mean
age = 34 years) received a single oral dose of placebo or 5, 20,
60, 150, 300, 600 or 1,000 mg of OPM-101, with one cohort dedicated
to the high-fat meal effect and another to the gender effect, also
receiving 150mg.
- In the MAD part of the trial, 32 HV (mean
age = 36 years) received an oral dose of 75, 150 or 300 mg of
OPM-101 or placebo twice daily for 14 consecutive days, including a
cohort dedicated to the gender effect, receiving 150mg twice a
day.
Safety assessments (physical examination, vital signs, blood
tests, ECGs, holters) were performed regularly throughout the
trial. In addition, blood samples were collected to measure
circulating concentrations of OPM-101 and engagement of RIPK2, the
pharmacological target of OPM-101 (measured by inhibition of
stimulated TNFα production).
Robust safety data, no toxicity on cardiac parameters
OPM-101 was very well tolerated after administration in SAD and
MAD. No severe or serious adverse events were reported, and no
volunteer discontinued the study. All treatment-emergent adverse
events considered to be at least possibly drug- and study-related
were mild to moderate. Fourteen healthy volunteers (13.5%) reported
a total of 18 adverse events considered related to study treatment
(OPM-101 or placebo). Among them, 12 healthy volunteers (15%)
reported a total of 15 adverse events considered to be related to
OPM-101, the majority of which were headaches. 80% of these events
were mild and 20% moderate. There were no clinically significant
changes in safety-related laboratory tests reported during the
treatment periods for all OPM-101 dose cohorts included in the
analysis, with the exception of one volunteer who received a dose
of 150mg twice daily and experienced a moderate (3x normal)
increase in ALT (liver enzyme) during MAD, leading to
discontinuation of her treatment on the morning of study day 12. In
this volunteer, further increases in liver proteins were not
observed.
Cardiac function was monitored in detail with daily 12-lead
ECGs, particularly at the time of peak circulating concentrations.
24-hour ECG recordings (holters) and cardiac ultrasound were also
performed. All these examinations showed normal results, without
any relation to circulating OPM-101 concentrations, and without any
clinically significant changes. This type of monitoring is common
at this stage of development, particularly for kinase inhibitors.
The results obtained make OPM-101 a first-rate molecule in this
field.
Promising pharmacokinetic and pharmacodynamic results
OPM-101 significantly inhibits the RIPK2 pathway. Target
engagement kinetics and pharmacodynamic results showed a fast and
marked onset of inhibitory effect, already observed 2-6h after
first administration, with maximal inhibition of 90-100%, and
minimal inhibition of 65%-85% maintained over 14 days of
dose-dependent administration. Inhibition remained marked (50% to
80%) 24 hours after the last administration on day 14 in the MAD
part.
The pharmacokinetic parameters of OPM-101 showed consistent
results between the SAD and MAD parts, and characteristics suitable
for use in patients. OPM-101 is rapidly absorbed, with a Tmax
observed between 2-4h, a terminal half-life of around 12h,
steady-state reached after 3-4 days and dose-dependent exposure
with repeated administration.
On the basis of the PK/PD relationship determined from the
results of the MAD part of the study, we anticipate that a very
significant target commitment (≥80%) can be achieved and maintained
with a residual OPM-101 plasma concentration (Cmin) in the range
150-300 ng/mL. In addition, population pharmacokinetic modelling
has enabled us to simulate different dose regimes for a future
clinical study, and the target dose could be 150mg twice daily.
OPM and Professor Peyrin-Biroulet, presented the phase 1 results
at the United European Gastroenterology Week (UEGW) 2024 held from
October 12 to 15, 2024 in Vienna, Austria.
Based on the results presented today, OPM plans to submit a
protocol for a phase 1b/2a clinical study in the fourth quarter of
2024.
"We are very pleased with the progress and results of this
clinical trial with OPM-101, which provided convincing results for
all primary, secondary and exploratory endpoints included in this
study," said Philippe Genne, Chief Executive Officer of OPM.
"We are pleased to demonstrate the safety of our candidate and the
strong pharmacodynamic correlation that exists. High target
engagement is demonstrated at tolerated doses of OPM-101 throughout
the treatment period. The modulation of TNFα production ex vivo can
be considered as a key biomarker of target engagement for future
clinical trials. The clinical results reported today not only
highlight the consistency with the immunomodulatory effect of
OPM-101 observed in preclinical studies, but also validate OPM-101
as a safe and effective inhibitor of the RIPK2 pathway. We are
currently in the process of identifying with our scientists and
clinicians’ experts the first clinical indication that we will
explore in a phase 1b/2a study before the end of the year in order
to provide a first clinical proof of concept in a patient
population capable of generating significant added value for our
asset".
"These complete Phase 1 results confirm and validate OPM-101 as
a highly specific, effective and well-tolerated inhibitor of the
RIPK2 immune pathway," added Jan Hoflack, Deputy CEO and Chief
Scientific Officer of OPM. "The field related to this
therapeutic approach is currently booming with new high quality
preclinical and clinical scientific publications mentioning a
potential role for an inhibitor like OPM-101 in multiple
immuno-oncology indications, in addition to the already
well-established rational for the treatment of IBD and other
inflammatory diseases. Our team is currently working to validate
the different therapeutic options available for OPM-101, with the
aim of launching a proof-of-concept clinical trial in relevant
patients rapidly and efficiently before the end of the year. The
current idea of a safe and effective RIPK2 inhibitor like OPM-101
suggests significant potential in both IBD and immuno-oncology, two
of today's largest pharmaceutical markets with significant unmet
needs".
About Oncodesign Precision Medicine (OPM)
Oncodesign Precision Medicine (OPM), founded in 2022, is a
biopharmaceutical company specializing in precision medicine,
dedicated to the discovery of treatments for resistant and
metastatic cancers.
OPM currently has two kinase inhibitors in clinical trials:
OPM-101, for the treatment of chronic immuno-inflammatory digestive
diseases and immuno-oncology, demonstrated high target engagement
and absence of toxicity in its phase I trial in healthy volunteers.
Phase Ib/IIa is scheduled to start at the beginning of 2025.
OPM-201, licensed to Servier for the treatment of Parkinson's
disease, completed its Phase I trial in healthy volunteers this
year, with Phase II scheduled to start in 2025. Finally, a third
kinase inhibitor, OPM-102, targeting oncology, is in preclinical
development.
These three molecules come from the Nanocyclix® technology
platform, which enables the design and selection of small
macrocyclic kinase inhibitors that are highly effective and
selective. Today, we have 12,000 molecules in our library,
providing a unique, annotated database on a multitude of parameters
essential to the development of this type of product. We use AI
approaches to accelerate the discovery of drug candidates while
reducing the cost of this phase.
OPM's two other technology platforms are:
- OncoSNIPER, for the selection of therapeutic targets using
artificial intelligence, in partnership with Servier for the search
of targets in pancreatic cancer,
- PROMETHE® for the design and selection of radiolabeled
biological molecules for systemic radiotherapy, for which we have
signed a partnership agreement with Navigo and are currently
discussing partnerships with other vectorization companies.
OPM, co-founded by Philippe Genne, Jan Hoflack and Karine
Lignel, is based in Dijon, in the heart of the university and
hospital cluster, and has 20 employees.
Further information: oncodesign.com
View source
version on businesswire.com: https://www.businesswire.com/news/home/20241022454432/en/
OPM Karine Lignel Deputy General Manager Tel: +33 (0)3 80
78 41 93 investisseurs@oncodesign.com
NewCap Investor Relations Mathilde Bohin / Alban Dufumier
Tel: +33 (0)1 44 71 94 95 oncodesign@newcap.eu
NewCap Media Relations Arthur Rouillé Tel: +33 (0)1 44 71
00 15 oncodesign@newcap.eu
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